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The effect of low-dose naltrexone on solid Ehrlich carcinoma in mice: The role of OGFr, BCL2, and immune response.
Int Immunopharmacol 2020; 78:106068II

Abstract

AIMS

Cancer is a major worldwide health problem. Cancer cells express opioid growth factor (OGF) which controls their growth. Naltrexone in low dose (LDN) blocks opioid receptors intermittently and controls the replication of cancer cells. The aim of this study was to investigate the effect of LDN and its chemotherapeutic additive effect on the growth of solid Ehrlich carcinoma in mice with focus on the OGFr and immune responses.

MAIN METHODS

Sixty female Swiss albino mice were assigned into 5 groups (n: 12 mice each): (i): normal control, (ii): Solid Ehrlich carcinoma (SEC), (iii): SEC treated with LDN, (iv): SEC treated with 5-fluorouracil (5-FU), (v): SEC treated with LDN + 5-FU. All drugs were started when the tumor became palpable on 9th day. At the end of the study animals were sacrificed, blood and tissue samples were collected. Tumor weight and volume were measured. Splenocytes and myeloid derived suppressor cells (MDSC) were counted. Tumor expression of opioid growth factor receptors (OGFr), serum level of IFN-γ, tumor histopathology (H&E) and immunohistochemistry staining of p21, p53, Bcl2 were assessed.

KEY FINDINGS

All drug-treated groups showed reduction in tumor weight and volume, significant increase of splenocyte with tendency to reduce MDSC cell counts. LDN led to significant increase in OGFr both in solo and in combination with 5FU. Serum IFN-γ is significantly increased by LDN but decreased by 5-FU. Also, LDN and 5FU increased immunehistochemical staining of p21 while decreased immunostaining of Bcl2. In animals treated with a combination of LDN and 5FU a maximal downregulation of the antiapoptotic mediator BCL2 was observed.

SIGNIFICANCE

The current study suggested that LDN may play a role in inhibiting cancer cell growth and highlights the possibility of promising combination with cancer chemotherapeutics, which guarantee further clinical studies for approval.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt.Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt; Department of Pharmacology, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia. Electronic address: sabah.elghaish@med.tanta.edu.eg.Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt.Department of Zoology, Faculty of Science, Tanta University, Tanta, Egypt.Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta, Egypt; Department of Clinical Pharmacology, Faculty of Medicine, Bisha University, Bisha, Saudi Arabia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31835085

Citation

Aboalsoud, Alshimaa, et al. "The Effect of Low-dose Naltrexone On Solid Ehrlich Carcinoma in Mice: the Role of OGFr, BCL2, and Immune Response." International Immunopharmacology, vol. 78, 2020, p. 106068.
Aboalsoud A, El-Ghaiesh SH, Abd Elmonem FF, et al. The effect of low-dose naltrexone on solid Ehrlich carcinoma in mice: The role of OGFr, BCL2, and immune response. Int Immunopharmacol. 2020;78:106068.
Aboalsoud, A., El-Ghaiesh, S. H., Abd Elmonem, F. F., Salem, M. L., & Abdel Rahman, M. N. (2020). The effect of low-dose naltrexone on solid Ehrlich carcinoma in mice: The role of OGFr, BCL2, and immune response. International Immunopharmacology, 78, p. 106068. doi:10.1016/j.intimp.2019.106068.
Aboalsoud A, et al. The Effect of Low-dose Naltrexone On Solid Ehrlich Carcinoma in Mice: the Role of OGFr, BCL2, and Immune Response. Int Immunopharmacol. 2020;78:106068. PubMed PMID: 31835085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of low-dose naltrexone on solid Ehrlich carcinoma in mice: The role of OGFr, BCL2, and immune response. AU - Aboalsoud,Alshimaa, AU - El-Ghaiesh,Sabah H, AU - Abd Elmonem,Fleur F, AU - Salem,Mohammed L, AU - Abdel Rahman,Mohamed N, Y1 - 2019/12/10/ PY - 2019/08/06/received PY - 2019/11/11/revised PY - 2019/11/19/accepted PY - 2019/12/14/pubmed PY - 2019/12/14/medline PY - 2019/12/14/entrez KW - 5-flurouracil KW - Bcl2 KW - Cancer KW - Ehrlich carcinoma KW - IFN-γ KW - Low dose naltrexone KW - MDSC KW - OGFr KW - P21 KW - P53 KW - Splenocytes SP - 106068 EP - 106068 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 78 N2 - AIMS: Cancer is a major worldwide health problem. Cancer cells express opioid growth factor (OGF) which controls their growth. Naltrexone in low dose (LDN) blocks opioid receptors intermittently and controls the replication of cancer cells. The aim of this study was to investigate the effect of LDN and its chemotherapeutic additive effect on the growth of solid Ehrlich carcinoma in mice with focus on the OGFr and immune responses. MAIN METHODS: Sixty female Swiss albino mice were assigned into 5 groups (n: 12 mice each): (i): normal control, (ii): Solid Ehrlich carcinoma (SEC), (iii): SEC treated with LDN, (iv): SEC treated with 5-fluorouracil (5-FU), (v): SEC treated with LDN + 5-FU. All drugs were started when the tumor became palpable on 9th day. At the end of the study animals were sacrificed, blood and tissue samples were collected. Tumor weight and volume were measured. Splenocytes and myeloid derived suppressor cells (MDSC) were counted. Tumor expression of opioid growth factor receptors (OGFr), serum level of IFN-γ, tumor histopathology (H&E) and immunohistochemistry staining of p21, p53, Bcl2 were assessed. KEY FINDINGS: All drug-treated groups showed reduction in tumor weight and volume, significant increase of splenocyte with tendency to reduce MDSC cell counts. LDN led to significant increase in OGFr both in solo and in combination with 5FU. Serum IFN-γ is significantly increased by LDN but decreased by 5-FU. Also, LDN and 5FU increased immunehistochemical staining of p21 while decreased immunostaining of Bcl2. In animals treated with a combination of LDN and 5FU a maximal downregulation of the antiapoptotic mediator BCL2 was observed. SIGNIFICANCE: The current study suggested that LDN may play a role in inhibiting cancer cell growth and highlights the possibility of promising combination with cancer chemotherapeutics, which guarantee further clinical studies for approval. SN - 1878-1705 UR - https://www.unboundmedicine.com/medline/citation/31835085/The_effect_of_low-dose_naltrexone_on_solid_Ehrlich_carcinoma_in_mice:_The_role_of_OGFr,_BCL2,_and_immune_response L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(19)31738-2 DB - PRIME DP - Unbound Medicine ER -